The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). Summary and Background Data: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. Patients and Methods: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models

Background and aim Transplantation (Tx) of non-vascularized rectus fascia (NVRF) is a valid option in solid organ transplant recipients to avoid open abdomen after Tx. To extrapolate this technique for non-Tx patients, we investigated in a preclinical rabbit model the feasibility of transplanting NVRF in a syngeneic (Syn) versus allogeneic (Allo) strain without using immunosuppression (IS). Short-term outcome was evaluated after 4 weeks. Material and methods A validated rabbit model of NVRF Tx was used comparing 6 Syn New Zealand White (NZW) rabbits versus 6 Allo Mixed breed to NZW Tx without IS. Animals were macroscopically analyzed at harvesting after 4 weeks for graft integration, herniation, adhesions, seroma, hematoma, and surgical site infections. Histological and immunohistochemical analysis was performed to assess inflammatory cell reaction and neovascularization. Mechanical testing was performed to assess the thickness, stiffness and strength. Results Results showed similar sufficient macroscopic ingrowth of the NVRF in both groups. At the histological level, cell infiltration suggested a clearing reaction more than a rejection-based inflammation, which was more pronounced in the Allo group. No significant differences were seen concerning mechanical properties. Conclusions In a validated rabbit model of NVRF Tx, we showed that Tx was possible in an Allo strain without the need for IS, resulting in satisfying short term inflammatory and mechanical outcomes. Longer-term experiments are needed to evaluate the effect of graft integration and possible hernia development.

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